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Abstract

Background Clinical trials support the belief that high-density lipoprotein (HDL) is atheroprotective. However, recent studies suggest that some patients with, or at risk for, atherosclerosis may have dysfunctional HDL despite normal cholesterol content of HDL (HDL-C). We investigated whether measures of HDL function, such as cholesterol efflux through the ABCA1 transporter or the ability of HDL to prevent oxidation using the Oxygen Radical Absorbance Capacity (ORAC), may demonstrate abnormalities in HDL function in women at risk for atherosclerosis because of sedentary lifestyle and obesity.

Methods Fifty-four women [28 Caucasian, 26 African American; BMI 34.3±6.9 kg/m2 (mean±SD), range 25.3–54.8 kg/m2; age 46±11, range 26– 66 y] were enrolled in a worksite wellness program at the National Institutes of Health. Cholesterol efflux was assessed in BHK cells expressing the ABCA1 transporter and in control cells not expressing the ABCA1 transporter after a 18 hour incubation with 1% diluted serum. ORAC values were determined on isolated HDL from 10 samples with the lowest cholesterol efflux values and 10 samples from women in this cohort matched by age, race, and HDL-C levels who served as controls. ORAC was assessed by measuring capacity of HDL to inhibit oxygen radicals produced by AAPH every minute over 2 hours, and normalized to HDL content.

Results Cholesterol efflux ranged from 8.2 to 22.5%/18hrs for the entire cohort. The 10 samples with the lowest cholesterol efflux (9.4±0.9%/18 hours) had an ORAC value of 4.3 μM (range: 0.2– 6.3 μM), as opposed to the control group (efflux 13.8±3.0%, P =0.001) with ORAC of 9.8 μM (range: 3.4–18.1 μM), P<0.001. Significant differences in oxidation were also observed when ORAC values were normalized to HDL content (8.0±4.2% vs. 18.6±7.7% control, P=0.0005). HDL-C levels were similar for the two groups (57 mg/dL vs. 53 mg/dL, P=0.6), as were levels of prebeta-1 and HDL 2b subfraction (both P > 0.34).

Conclusion Concomittant low cholesterol efflux and reduced ability of HDL to prevent oxidation in a subset of obese women suggests presence of dysfunctional HDL despite normal HDL-C levels and absence of differences in HDL subfractions, and may contribute to atherosclerosis risk.